Methyltransferase 3A-mediated promoter methylation represses retinoic acid receptor responder 3 expression in basal-like breast cancer

Retinoic acid receptor responder 3(RARRES3)has been characterized as a tumor suppressor in multiple types of cancer.This study aimed to examine the expression profile of RARRES3 across the PAM50 subtypes of breast cancer.The DNA methylation status of RARRES3 was checked in the basal-like subtype,and the underlying mechanisms of its dysregulation were explored.RNA-sequencing(seq)and methylation data from The Cancer Genome Atlas were used for in-silico analysis.Basal-like representative SUM149 and MDA-MB-468 cell lines were used for in vitro and in vivo studies.Compared to tumor-adjacent normal tissues,only the basal-like tumor tissues had significantly downregulated RARRES3 expression.The methylation level of four CpG sites in the promoter region showed a strong negative correlation with RARRES3 expression.The gene coding for DNA methyltransferase 3A(DNMT3A)had consistent positive correlations with the methylation of the CpG sites.Chromatin Immunoprecipitation-quantitative polymerase chain-reaction and bisulfite sequencing PCR showed that DNMT3A could bind to the promoter region of RARRES3 and promote methylation of the CpG sites within the region.DNMT3A knockdown significantly restored RARRES3 expression at the mRNA and protein level in the two cell lines.CCK-8,colony formation,and flow cytometric analysis showed that RARRES3 overexpression attenuated the growth-promoting effects of DNMT3A overexpression and also weakened the DNMT3A overexpression-induced activation of ERK1/2 and PI3K/AKT signaling.In summary,this study revealed that DNMT3A enhances promoter methylation of the RARRES3 gene and suppresses its transcription in basal-like breast cancer.The DNMT3A-RARRES3 signaling pathway might be a potential target for the treatment of this tumor subtype.

Guidelines for the diagnosis and treatment of acute pancreatitis in China (2021)

Acute pancreatitis(AP)is a common acute abdominal condition of the digestive system.In recent years,treatment concepts,methods,and strategies for the diagnosis of AP have advanced,and this has played an important role in promoting the standardization of AP diagnosis and treatment and improving the treatment quality of AP patients.On the basis of previous guidelines and expert consensus,this guideline adopts an evidence-based,problem-based expression;synthesizes important clinical research data at home and abroad in the most recent 5 years;and forms 29 recommendations through multidisciplinary expert discussion,including diagnosis,treatment,and follow-up.It is expected to provide evidence support for the treatment of AP in the clinical setting in China.

The current surgical treatment of pancreatic neuroendocrine neoplasms in China: a national wide cross-sectional study

Objective:The aim of this study is to investigate the current status of the diagnosis and treatment of patients with pancreatic neuroendocrine neoplasms(pNENs)undergoing surgery in China.Methods:This is a multicenter cross-sectional study performed in China.Data from patients with pNENs undergoing surgery at 33 high-volume medical centers,where the number of pancreatectomies exceeds 20 cases per year,were collected and analyzed between March 1,2016 and February 28,2017.Results:In total,392 patients with pNENs were enrolled.The male to female ratio was 1.4.The majority of patients were aged between 40 and 70 years.65.6%of the patients had non-functional tumors.Among those with functional tumors,the percentages of insulinomas,gastrinomas,glucagonomas,and vasoactive intestinal peptide-secreting tumors were 94.8%,1.5%,2.2%,and 1.5%,respectively.Multidisciplinary team(MDT)discussion was conducted for 39.0%of the patients.Minimally invasive surgery was performed on 31.1%of the 392 patients.The incidence of grade B/C pancreatic fistula formation was 4.4%.A total of 89.0%of the surgeries achieved R0 resection,and 41.6%of the tumors were well differentiated.Lymph node metastasis was present in 8.9%of the patients.The percentages of patients with grades G1,G2,and G3 disease were 49.2%,45.7%,and 5.1%,respectively.Conclusion:This multicenter cross-sectional study systematically presents the current status of the diagnosis and treatment of patients with pNENs undergoing surgery in China.MDT consultation for pNENs has not been widely implemented in China.Although the incidence of surgical complications is relatively low,minimally invasive procedures should be further promoted.This study shows us how to improve the outcomes of these patients.

The current surgical treatment of pancreatic cancer in China: a national wide cross-sectional study

Objective: The aim of this study is to investigate the current status of pancreatic cancer patients undoing surgical treatment in China and to find ways to improve the survival of these patients in the future. Methods: This study is a national, multicenter, cross-sectional study in China. Information regarding pancreatic cancer patients undergoing surgical treatment from 34 high-volume tertiary IIIA level hospitals was collected and analyzed from the March 1, 2016 to the February 28, 2017. Results: In total, 2200 pancreatic cancer patients were enrolled from 34 tertiary IIIA level hospitals in 16 provinces across China. The male-to-female ratio was 1.5. More than 80% of the patients were between 50 and 70 years old. The top 4 symptoms were epigastric discomfort, abdominal pain, jaundice, and weight loss. Carbohydrate antigen 19-9 and carcinoembryonic antigen were elevated in 70.9% and 27.1% of patients, respectively. A multidisciplinary team (MDT) discussion was carried out for 35.0% of patients before surgery. The proportion of minimally invasive pancreatic surgeries was approximately 20%. A total of 83.4% of the operations achieved R0 resection, and the incidence of grade 3/4 postoperative complications was 7.7%. Only 13.4% of the patients received postoperative adjuvant chemotherapy. The percentage of pathological stage I tumors was only 24.5%. Conclusion: The majority of pancreatic cancer patients undergoing surgical resection in China are in an advanced stage. The MDT consultations for pancreatic cancer have not been widely carried out. R0 resection has been achieved in most cases, with relatively low incidence of serious complications, but minimally invasive pancreatic surgery should be further promoted. The application of postoperative chemotherapy remains low. This national, multicentre, cross-sectional study comprehensively presents the current status of pancreatic cancer patients undergoing surgical treatment and shows the road to improve survival of these patients in the future.

Guidelines for the diagnosis and treatment of pancreatic cancer in China (2021)

The incidence of pancreatic cancer has been rising worldwide,and its clinical diagnosis and treatment remain a great challenge.To present the update and improvements in the clinical diagnosis and treatment of pancreatic cancer in recent years,Chinese Pancreatic Association,the Chinese Society of Surgery,Chinese Medical Association revised the Guidelines for the Diagnosis and Treatment of Pancreatic Cancer in China(2014)after reviewing evidence-based and problem-oriented literature published during 2015-2021,mainly focusing on highlight issues regarding diagnosis and surgical treatment of pancreatic cancer,conversion strategies for locally advanced pancreatic cancer,treatment of pancreatic cancer with oligo metastasis,adjuvant and neoadjuvant therapy,standardized processing of surgical specimens and evaluation of surgical margin status,systemic treatment for unresectable pancreatic cancer,genetic testing,as well as postoperative follow up of patients with pancreatic cancer.Forty recommendation items were finally proposed based on the above issues,and the quality of evidence and strength of recommendations were graded using the Grades of Recommendation,Assessment,Development,and Evaluation system.This guideline aims to standardize the clinical diagnosis and therapy,especially surgical treatment of pancreatic cancer in China,and further improve the prognosis of patients with pancreatic cancer.

Abdominal abscess caused by acute cholecystitis

A 54-year-old man presented with a 2-month history of painless swelling of the right abdomen that had persistent right epigastric pain radiating toward the dorsal shoulder,with no jaundice.He had a history of diabetes for 8 years and was taking metformin,a hypoglycemic drug.A clinical diagnosis of the abdominal abscess(Figure 1A,yellow arrow)caused by acute cholecystitis(Figure 1A,white arrow)was confirmed on abdominal Magnetic Resonance Imaging.